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Semin Neurol 2019; 39(02): 283-292
DOI: 10.1055/s-0039-1678583
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Autoimmune Encephalitides and Rapidly Progressive Dementias

Sarah F. Wesley
1   Department of Neurology, Yale School of Medicine, New Haven, Connecticut
,
Damien Ferguson
2   Academic Unit of Neurology, University of Dublin, Trinity College, Dublin 2, Ireland
› Author Affiliations
Further Information

Publication History

Publication Date:
29 March 2019 (online)

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Abstract

Rapidly progressive dementia (RPD) or cognitive decline is a common presenting complaint in neurology. While primary dementia is often a concern, other forms of reversible dementia must be thoroughly considered. This article focuses on the growing field of autoimmune encephalitis (AE) as it pertains to the differential diagnostic considerations in a work-up for RPD. Understanding clues in the history and examination is the first step in identifying patients with a potential autoimmune cause for RPD. While testing for infectious and toxic-metabolic etiologies is commonly preformed, it is necessary to consider early ancillary testing for AE in appropriate cases of RPD. Autoantibody testing in the spinal fluid and serum, brain imaging, and electroencephalography all form the first line of investigations for AE. Treatment options and strategies depend on the AE subtype and a number of individual patient considerations.

Keywords

autoimmune encephalitis - rapidly progressive dementia - autoimmune dementia

Disclosures

Sarah F. Wesley is a former editorial staff member for Neurology Resident and Fellow Section. She is currently a guest reviewer for Neurology without compensation. She also serves as a guest reviewer for Clinical Therapeutics and has received compensation.


Damien Ferguson has received travel grants from Biogen Idec for attendance at international conferences. He is currently enrolled in a PhD program funded by the Health Research Board of Ireland.


 

  • References

  • 1 Vale TC, Cardoso F. Chorea: a journey through history. Tremor Other Hyperkinet Mov (N Y) 2015; 5: 5
    PubMedSearch in Google Scholar
  • 2 Bigman DY, Bobrin BD. Von Economo's disease and postencephalitic parkinsonism responsive to carbidopa and levodopa. Neuropsychiatr Dis Treat 2018; 14: 927-931
    CrossrefPubMedSearch in Google Scholar
  • 3 Berger JR, Vilensky JA. Encephalitis lethargica (von Economo's encephalitis). Handb Clin Neurol 2014; 123: 745-761
    CrossrefPubMedSearch in Google Scholar
  • 4 Payer J, Petrovic T, Lisy L, Langer P. Hashimoto encephalopathy: a rare intricate syndrome. Int J Endocrinol Metab 2012; 10 (02) 506-514
    CrossrefPubMedSearch in Google Scholar
  • 5 Corsellis JA, Goldberg GJ, Norton AR. “Limbic encephalitis” and its association with carcinoma. Brain 1968; 91 (03) 481-496
    CrossrefPubMedSearch in Google Scholar
  • 6 Dalmau J, Geis C, Graus F. Autoantibodies to synaptic receptors and neuronal cell surface proteins in autoimmune diseases of the central nervous system. Physiol Rev 2017; 97 (02) 839-887
    CrossrefPubMedSearch in Google Scholar
  • 7 Höftberger R, Titulaer MJ, Sabater L. , et al. Encephalitis and GABAB receptor antibodies: novel findings in a new case series of 20 patients. Neurology 2013; 81 (17) 1500-1506
    CrossrefPubMedSearch in Google Scholar
  • 8 Dalmau J, Lancaster E, Martinez-Hernandez E, Rosenfeld MR, Balice-Gordon R. Clinical experience and laboratory investigations in patients with anti-NMDAR encephalitis. Lancet Neurol 2011; 10 (01) 63-74
    CrossrefPubMedSearch in Google Scholar
  • 9 Lai M, Hughes EG, Peng X. , et al. AMPA receptor antibodies in limbic encephalitis alter synaptic receptor location. Ann Neurol 2009; 65 (04) 424-434
    CrossrefPubMedSearch in Google Scholar
  • 10 Lancaster E. The diagnosis and treatment of autoimmune encephalitis. J Clin Neurol 2016; 12 (01) 1-13
    CrossrefPubMedSearch in Google Scholar
  • 11 Irani SR, Michell AW, Lang B. , et al. Faciobrachial dystonic seizures precede Lgi1 antibody limbic encephalitis. Ann Neurol 2011; 69 (05) 892-900
    CrossrefPubMedSearch in Google Scholar
  • 12 Peterson K, Rosenblum MK, Kotanides H, Posner JB. Paraneoplastic cerebellar degeneration. I. A clinical analysis of 55 anti-Yo antibody-positive patients. Neurology 1992; 42 (10) 1931-1937
    CrossrefPubMedSearch in Google Scholar
  • 13 Vernino S, Lennon VA. New Purkinje cell antibody (PCA-2): marker of lung cancer-related neurological autoimmunity. Ann Neurol 2000; 47 (03) 297-305
    CrossrefPubMedSearch in Google Scholar
  • 14 Geschwind MD, Haman A, Miller BL. Rapidly progressive dementia. Neurol Clin 2007; 25 (03) 783-807 , vii
    CrossrefPubMedSearch in Google Scholar
  • 15 Geschwind MD, Shu H, Haman A, Sejvar JJ, Miller BL. Rapidly progressive dementia. Ann Neurol 2008; 64 (01) 97-108
    CrossrefPubMedSearch in Google Scholar
  • 16 Day GS, Tang-Wai DF. When dementia progresses quickly: a practical approach to the diagnosis and management of rapidly progressive dementia. Neurodegener Dis Manag 2014; 4 (01) 41-56
    CrossrefPubMedSearch in Google Scholar
  • 17 Paterson RW, Takada LT, Geschwind MD. Diagnosis and treatment of rapidly progressive dementias. Neurol Clin Pract 2012; 2 (03) 187-200
    CrossrefPubMedSearch in Google Scholar
  • 18 Rosenbloom MH, Atri A. The evaluation of rapidly progressive dementia. Neurologist 2011; 17 (02) 67-74
    CrossrefPubMedSearch in Google Scholar
  • 19 Heckman GA, Hawkins C, Morris A, Burrows LL, Bergeron C. Rapidly progressive dementia due to Mycobacterium neoaurum meningoencephalitis. Emerg Infect Dis 2004; 10 (05) 924-927
    CrossrefPubMedSearch in Google Scholar
  • 20 Valcour V, Haman A, Cornes S. , et al; Vanderbilt Continuing Medical Education online. A case of enteroviral meningoencephalitis presenting as rapidly progressive dementia. Nat Clin Pract Neurol 2008; 4 (07) 399-403
    CrossrefPubMedSearch in Google Scholar
  • 21 Habek M, Ozretić D, Zarković K, Djaković V, Mubrin Z. Unusual cause of dementia in an immunocompetent host: toxoplasmic encephalitis. Neurol Sci 2009; 30 (01) 45-49
    CrossrefPubMedSearch in Google Scholar
  • 22 Papageorgiou SG, Kontaxis T, Bonakis A, Karahalios G, Kalfakis N, Vassilopoulos D. Rapidly progressive dementia: causes found in a Greek tertiary referral center in Athens. Alzheimer Dis Assoc Disord 2009; 23 (04) 337-346
    CrossrefPubMedSearch in Google Scholar
  • 23 Sala I, Marquié M, Sánchez-Saudinós MB. , et al. Rapidly progressive dementia: experience in a tertiary care medical center. Alzheimer Dis Assoc Disord 2012; 26 (03) 267-271
    CrossrefPubMedSearch in Google Scholar
  • 24 Grau-Rivera O, Gelpi E, Nos C. , et al; Neurological Tissue Bank Collaborative Group. Clinicopathological correlations and concomitant pathologies in rapidly progressive dementia: a brain bank series. Neurodegener Dis 2015; 15 (06) 350-360
    CrossrefPubMedSearch in Google Scholar
  • 25 Neto AS, Neto HS, Simabukuro M. , et al. Rapidly progressive dementia in a neurologic unit of a tertiary hospital in Brazil. J Neurol Sci 2015; 357: E139
    PubMedSearch in Google Scholar
  • 26 Hale A, Geerling J, Schmolze D, Pfannl R, Karchmer AWA. A 63-year-old man with rapidly progressive dementia. Clin Infect Dis 2016; 63 (01) 138-139
    CrossrefPubMedSearch in Google Scholar
  • 27 Santana-Ramírez A, Esparza-Gutiérrez SV, Avila-Rodríguez P, Jiménez-Gómez JE, Vélez-Gómez E, Bañuelos-Gallo D. Aspergillosis of the central nervous system in a previously healthy patient that simulated Creutzfeldt-Jakob disease. Surg Neurol Int 2016; 7 (Suppl. 39) S940-S946
    CrossrefPubMedSearch in Google Scholar
  • 28 Anuja P, Venugopalan V, Darakhshan N. , et al. Rapidly progressive dementia: An eight year (2008-2016) retrospective study. PLoS One 2018; 13 (01) e0189832
    CrossrefPubMedSearch in Google Scholar
  • 29 Chandra SR, Raj P, Pai AR, Reddy N. A case of Whipple's disease: a very rare cause for rapidly progressive dementia. Indian J Psychol Med 2018; 40 (03) 280-283
    CrossrefPubMedSearch in Google Scholar
  • 30 Jungreis AC, Schaumburg HH. Encephalopathy from abuse of bismuth subsalicylate (Pepto-Bismol). Neurology 1993; 43 (06) 1265-1265
    PubMedSearch in Google Scholar
  • 31 Graus F, Titulaer MJ, Balu R. , et al. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol 2016; 15 (04) 391-404
    CrossrefPubMedSearch in Google Scholar
  • 32 Gresa-Arribas N, Titulaer MJ, Torrents A. , et al. Antibody titres at diagnosis and during follow-up of anti-NMDA receptor encephalitis: a retrospective study. Lancet Neurol 2014; 13 (02) 167-177
    CrossrefPubMedSearch in Google Scholar
  • 33 Shin YW, Lee ST, Park KI. , et al. Treatment strategies for autoimmune encephalitis. Ther Adv Neurol Disorder 2017; 11: 1756285617722347
    PubMedSearch in Google Scholar
  • 34 Mayo Clinic. Mayo Medical Laboratories. Test ID: DMS1. Dementia, autoimmune evaluation, serum. Available at: https://www.mayomedicallaboratories.com/test-catalog/Overview/48402 . Published 2017. Accessed August 01, 2018
    PubMed
  • 35 Mayo Clinic. Mayo Medical Laboratories. Test ID: DMC1. Dementia, autoimmune evaluation, spinal fluid. Available at: https://www.mayomedicallaboratories.com/test-catalog/Overview/48405 . Published 2014. Accessed August 01, 2018
    PubMed
  • 36 Lee SK, Lee ST. The laboratory diagnosis of autoimmune encephalitis. J Epilepsy Res 2016; 6 (02) 45-50
    CrossrefPubMedSearch in Google Scholar
  • 37 Ganesh A, Wesley SF. Practice current: when do you suspect autoimmune encephalitis and what is the role of antibody testing?. Neurol Clin Pract 2018; 8 (01) 67-73
    CrossrefPubMedSearch in Google Scholar
  • 38 Waters P, Pettingill P, Lang B. Detection methods for neural autoantibodies. Handb Clin Neurol 2016; 133: 147-163
    PubMedSearch in Google Scholar
  • 39 Graus F, Keime-Guibert F, Reñe R. , et al. Anti-Hu-associated paraneoplastic encephalomyelitis: analysis of 200 patients. Brain 2001; 124 (Pt 6): 1138-1148
    CrossrefPubMedSearch in Google Scholar
  • 40 Luque FA, Furneaux HM, Ferziger R. , et al. Anti-Ri: an antibody associated with paraneoplastic opsoclonus and breast cancer. Ann Neurol 1991; 29 (03) 241-251
    CrossrefPubMedSearch in Google Scholar
  • 41 Pittock SJ, Lucchinetti CF, Lennon VA. Anti-neuronal nuclear autoantibody type 2: paraneoplastic accompaniments. Ann Neurol 2003; 53 (05) 580-587
    CrossrefPubMedSearch in Google Scholar
  • 42 Chan KH, Vernino S, Lennon VA. ANNA-3 anti-neuronal nuclear antibody: marker of lung cancer-related autoimmunity. Ann Neurol 2001; 50 (03) 301-311
    CrossrefPubMedSearch in Google Scholar
  • 43 Cross SA, Salomao DR, Parisi JE. , et al. Paraneoplastic autoimmune optic neuritis with retinitis defined by CRMP-5-IgG. Ann Neurol 2003; 54 (01) 38-50
    CrossrefPubMedSearch in Google Scholar
  • 44 Yu Z, Kryzer TJ, Griesmann GE, Kim K, Benarroch EE, Lennon VA. CRMP-5 neuronal autoantibody: marker of lung cancer and thymoma-related autoimmunity. Ann Neurol 2001; 49 (02) 146-154
    CrossrefPubMedSearch in Google Scholar
  • 45 Dalmau J, Graus F, Villarejo A. , et al. Clinical analysis of anti-Ma2-associated encephalitis. Brain 2004; 127 (Pt 8): 1831-1844
    CrossrefPubMedSearch in Google Scholar
  • 46 Bernal F, Shams'ili S, Rojas I. , et al. Anti-Tr antibodies as markers of paraneoplastic cerebellar degeneration and Hodgkin's disease. Neurology 2003; 60 (02) 230-234
    CrossrefPubMedSearch in Google Scholar
  • 47 de Graaff E, Maat P, Hulsenboom E. , et al. Identification of delta/notch-like epidermal growth factor-related receptor as the Tr antigen in paraneoplastic cerebellar degeneration. Ann Neurol 2012; 71 (06) 815-824
    CrossrefPubMedSearch in Google Scholar
  • 48 McKeon A, Tracy JA. GAD65 neurological autoimmunity. Muscle Nerve 2017; 56 (01) 15-27
    CrossrefPubMedSearch in Google Scholar
  • 49 Gagnon MM, Savard M, Mourabit Amari K. Refractory status epilepticus and autoimmune encephalitis with GABAAR and GAD65 antibodies: a case report. Seizure 2016; 37: 25-27
    CrossrefPubMedSearch in Google Scholar
  • 50 Dalmau J, Tüzün E, Wu HY. , et al. Paraneoplastic anti-N-methyl-D-aspartate receptor encephalitis associated with ovarian teratoma. Ann Neurol 2007; 61 (01) 25-36
    CrossrefPubMedSearch in Google Scholar
  • 51 Titulaer MJ, McCracken L, Gabilondo I. , et al. Late-onset anti-NMDA receptor encephalitis. Neurology 2013; 81 (12) 1058-1063
    CrossrefPubMedSearch in Google Scholar
  • 52 Boronat A, Sabater L, Saiz A, Dalmau J, Graus F. GABA(B) receptor antibodies in limbic encephalitis and anti-GAD-associated neurologic disorders. Neurology 2011; 76 (09) 795-800
    CrossrefPubMedSearch in Google Scholar
  • 53 Höftberger R, van Sonderen A, Leypoldt F. , et al. Encephalitis and AMPA receptor antibodies: novel findings in a case series of 22 patients. Neurology 2015; 84 (24) 2403-2412
    CrossrefPubMedSearch in Google Scholar
  • 54 Lai M, Huijbers MG, Lancaster E. , et al. Investigation of LGI1 as the antigen in limbic encephalitis previously attributed to potassium channels: a case series. Lancet Neurol 2010; 9 (08) 776-785
    CrossrefPubMedSearch in Google Scholar
  • 55 van Sonderen A, Schreurs MW, Wirtz PW, Sillevis Smitt PA, Titulaer MJ. From VGKC to LGI1 and Caspr2 encephalitis: the evolution of a disease entity over time. Autoimmun Rev 2016; 15 (10) 970-974
    CrossrefPubMedSearch in Google Scholar
  • 56 Sen A, Wang J, Laue-Gizzi H, Lee T, Ghougassian D, Somerville ER. Pathognomonic seizures in limbic encephalitis associated with anti-LGI1 antibodies. Lancet 2014; 383 (9933): 2018
    CrossrefPubMedSearch in Google Scholar
  • 57 van Sonderen A, Ariño H, Petit-Pedrol M. , et al. The clinical spectrum of Caspr2 antibody-associated disease. Neurology 2016; 87 (05) 521-528
    CrossrefPubMedSearch in Google Scholar
  • 58 Tobin WO, Lennon VA, Komorowski L. , et al. DPPX potassium channel antibody: frequency, clinical accompaniments, and outcomes in 20 patients. Neurology 2014; 83 (20) 1797-1803
    CrossrefPubMedSearch in Google Scholar
  • 59 Mayo Clinic. Mayo Medical Laboratories. Test ID: GD65S. Glutamic Acid decarboxylase (GAD65) antibody assay, serum. Available at: https://www.mayomedicallaboratories.com/test-catalog/Overview/81596 . Published 2017. Accessed August 01, 2018
    PubMed
  • 60 Malter MP, Elger CE, Surges R. Diagnostic value of CSF findings in antibody-associated limbic and anti-NMDAR-encephalitis. Seizure 2013; 22 (02) 136-140
    CrossrefPubMedSearch in Google Scholar
  • 61 Zhang T, Duan Y, Ye J. , et al. Brain MRI characteristics of patients with anti-N-methyl-D-aspartate receptor encephalitis and their associations with 2-year clinical outcome. AJNR Am J Neuroradiol 2018; 39 (05) 824-829
    CrossrefPubMedSearch in Google Scholar
  • 62 Kelley BP, Patel SC, Marin HL, Corrigan JJ, Mitsias PD, Griffith B. Autoimmune encephalitis: pathophysiology and imaging review of an overlooked diagnosis. AJNR Am J Neuroradiol 2017; 38 (06) 1070-1078
    CrossrefPubMedSearch in Google Scholar
  • 63 Schmitt SE, Pargeon K, Frechette ES, Hirsch LJ, Dalmau J, Friedman D. Extreme delta brush: a unique EEG pattern in adults with anti-NMDA receptor encephalitis. Neurology 2012; 79 (11) 1094-1100
    CrossrefPubMedSearch in Google Scholar
  • 64 Maskery MP, Hill J, Cain JR, Emsley HCA. The utility of FDG-PET/CT in clinically suspected paraneoplastic neurological syndrome: a literature review and retrospective case series. Front Neurol 2017; 8: 238
    CrossrefPubMedSearch in Google Scholar
  • 65 Gelfand JM, Genrich G, Green AJ, Tihan T, Cree BA. Encephalitis of unclear origin diagnosed by brain biopsy: a diagnostic challenge. JAMA Neurol 2015; 72 (01) 66-72
    CrossrefPubMedSearch in Google Scholar
  • 66 Gelfand J, Frederick C, Rabinowitz N. , et al. Development of a diagnostic decision tree for rapidly progressive dementia. Neurology 2016; 86 (Suppl_16): P5.182
    PubMedSearch in Google Scholar
  • 67 Boeck AL, Logemann F, Krauß T. , et al. Ovarectomy despite negative imaging in anti-NMDA receptor encephalitis: effective even late. Case Rep Neurol Med 2013; 2013: 843192
    PubMedSearch in Google Scholar
  • 68 Tang-Wai DF. A practical approach to the evaluation of a rapidly progressive dementia. 7th Canadian Conference on Dementia; 2013; Vancouver, Canada
    PubMed